The overall objective of the Neuropathology Core is to support and stimulate research on AD and age-related dementing disorders by supplying thoroughly evaluated brain specimens from AD patients and normal aged control subjects to investigators. The specific aims of the Neuropathology Core are to use our Rapid Autopsy Team to perform short postmortem interval PMI autopsies using a standardized protocol on longitudinally followed patients with AD and other age-related dementing disorders and cognitively normal aged, longitudinally followed, control subjects. The core will maintain a bank of brain specimens cerebrospinal fluid and synaptosome preparations from our short PMI autopsied subjects. The core will provide postmortem diagnosis, neurofibrillary tangle, neuritic and diffuse plaque quantification in six brain regions and slot-blot immunochemistry analysis of synaptophysin in multiple brain regions for investigator use. It will correlate the clinical, neuropsychological and neuropathological features of demented and control subjects in conjunction with the Clinical Core and will evaluate the effectiveness and validity of the neuropathological guidelines for the diagnosis of AD developed by the National Institute of Aging-Reagan Institute Working Group. The Neuropathology Core will emphasize the alterations present in the brain in our longitudinally followed normal aged control group, especially those with Mild Cognitive Impairment and early AD. Emphasis also will be placed on the morphological substrate of brain reserve in subjects resistant to dementia. Specimens for the unbiased stereological method will be prepared from the hippocampus and entorhinal cortex for investigator use. The core supports two UK AD program project grants, several R01 AD related grants, and two longitudinal neuroepidemiologic studies, the NUN Study and the Honolulu-Asian Aging Study, both with autopsy end points.